Laboratory for Langerhans Cell Research

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Research Interest

Dendritic cells (DC) are key immune regulators and in the periphery, such as the skin, they act as sentinels of the immune system. Their main function is antigen capture and presentation to T cells, hence on one side they can generate immunity and on the other side maintain peripheral tolerance to self-antigens. Moreover, DC function as a bridge between innate and adaptive immunity and are not merely limited to pathogen recognition, they also contribute to allergy, autoimmunity and cancer. Persistence of tumors is commonly accompanied by induction of tolerance against tumor specific antigens leading to immune evasion of the tumor. In fact, DC are promising targets for immunotherapy, and thus, used in clinical trials for treatment of cancer and autoimmunity, especially in combination therapy.

Our working group is interested in deciphering the role of DC subtypes in the skin immune system with special focus on tumor immunity. In an attempt to advance DC-based immunotherapy, we need to understand how skin DC biology and function are affected by tumor development.

Research focus:

• Investigation of the functional properties of the various skin DC subtypes in the induction of CD4+ and CD8+ T cell response
• Study differences in skin DC response to tumor development versus autoimmunity (vitiligo)
• Evaluation of the potential of DC-based immunotherapy together with tumor-targeted therapy, e.g. BRAF/MEK-inhibitor therapy
• Understanding the effects of tumor metabolism and aging on skin DC biology and function
• Advance skin immunization strategies for the treatment of cancer by DC-based targeting approaches
• Development of immunocompetent 3D-bioprinted human skin/melanoma-on chip-models

With diverse model systems, we aim to unravel the interaction and communication between DC subtypes and tumor cells with the ultimate goal to advance existing therapeutic strategies.

Copyright: P. Stoitzner/M. Hermann

Methodical approaches:

• In vitro human and mouse DC differentiation protocols
• Multiplex flow cytometry (Aurora) and imaging (MACSima), confocal microscopy, live cell imaging
• In vitro and in vivo immunoassays to investigate DC function
• Mouse models for melanoma
• Human skin explant models
• 3D-bioprinted human skin/melanoma models

Publications

Selected Publications:

1. Probst HC, Stoitzner P, et al. Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues. Eur J Immunol 2022 Dec 13. doi: 10.1002/eji.202249819. Online ahead of print. PMID: 36512638.
2. Hornsteiner F, Sykora MM, Tripp CH, Sopper S, Stoitzner P. Mouse dendritic cells and other myleoid subtypes in healthy lymph nodes and skin: 26-Color flow cytometry panel for immune phenotyping. Eur J Immunol 2022 Dec;52(12):2006-2009. doi: 10.1002/eji.202250004. PMID: 35944142
3. Stoitzner P, Romani N, Rademacher C, Probst HC, Mahnke K. Eur J Immunol 2022 Dec;52(12):1909-1924. doi: 10.1002/eji.202149515. PMID: 35598160.  Review.
4. Bellmann L, Strandt H, Zelle-Rieser C, Ortner D, Tripp CH, Schmid S, Rühl J, Cappellano G, Schaffenrath S, Prokopi A, Spoeck S, Seretis A, Del Frari B, Sigl S, Krapf J, Heufler C, Keler T, Münz C, Romani N, Stoitzner P. Targeted delivery of a vaccine protein to Langerhans cells in the human skin via the C-type lectin receptor Langerin.  Eur J Immunol 2022 Nov;52(11):1829-1841. doi: 10.1002/eji.202149670. PMID: 34932821. 
5. Prokopi A, Tripp CH, Tummers B, Hornsteiner F, Spoeck S, Crawford JC, Clements DR, Efremova M, Hutter K, Bellmann L, Cappellano G, Cadilha BL, Kobold S, Boon L, Ortner D, Trajanoski Z, Chen S, de Gruijl T, Idoyaga J, Green DR, Stoitzner P. Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy. J Immunotherap Cancer 2021. Jan;9(1): e000832. PMID: 33408092.
6. Bellmann L, Zelle-Rieser C, Milne P, Resteu A, Tripp CH, Hermann-Kleiter N, Zaderer V, Wilflingseder D, Hörtnagl P, Theochari M, Schulze J, Rentzsch M, Del Frari B, Collin M, Rademacher C, Romani N, Stoitzner P. Notch-mediated generation of monocyte-derived Langerhans cells: Phenotype and function. J Invest Dermatol 2021 Jan;141(1):84-96.e6. DOI: 10.1016/j.jid.2020.05.098.
7. Bellmann L, Cappellano G, Schachtl-Riess JF, Prokopi A, Seretis A, Ortner D, Tripp CH, Brinckerhoff CE, Mullins DW, Stoitzner P. A TLR7 agonist strengthens T and NK cell function during BRAF-targeted therapy in a preclinical melanoma model. Int J Cancer 2019. Mar 1; 146(5):1409-1420. PMID: 31702822.
8. Wamhoff EC, Schulze J, Bellmann L, Rentzsch M, Bachem G, Fuchsberger FF, Rademacher J, Hermann M, Del Frari B, van Dalen R, Hartmann D, van Sorge NM, Seitz O, Stoitzner P, Rademacher C. A specific, glycomimetic Langerin ligand for human Langerhans cell targeting. ACS Cent Sci 2019 May 22; 5(5):808-820. Epub 2019 May 22; 5(5):808-820. PMID: 31139717.
9. Ortner D, Tripp CH, Komenda K, Dubrac S, Zelger B, Hermann M, Doppler W, Tymoszuk PZ, Boon L, Clausen BE, Stoitzner P. Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis. Oncoimmunology 6, NO.2, e1260215. PMID: 28344868.
10. Clausen BE, Stoitzner P. Functional spezialisation of skin dendritic cell subsets in regulating T cell responses. Front Immunol 2015 Oct 22: 6:534. PMID: 26557117. Review
11. Mairhofer DG, Ortner D, Tripp CH, Schaffenrath S, Fleming V, Heger L, Komenda K, Reider D, Dudziak D, Chen S, Becker JC, Flacher V, Stoitzner P. Impaired gp100-specific CD8+ T cell responses in the presence of myeloid-derived supressor cells in a spontaneous mouse melanoma model. J Invest Dermatol 2015 Nov;135(11):2785-93. PMID: 26121214.
12. Flacher V, Tripp CH, Mairhofer DG, Steinman RM, Stoitzner P, Idoyaga J, Romani N. Murine Langerin+dermal dendritic cells prime CD8+ T cells while Langerhans cells induced cross-tolerance. EMBO Mol Med 2014. Aug 1;6(9):1191-204. PMID: 25085878.
13. Romani N, Clausen BE, Stoitzner P. Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev 2010 Mar;234(1):120-41 PMID:20193016. Review
14. Stoitzner P, Green LK, Jung JY, Price KM, Tripp CH, Malissen B, Kissenpfennig A, Hermans IF, Ronchese F. Tumor immunotherapy by epicutaneous immunization requires langerhans cells. J Immunol 2008 Feb 1;180(3):1991-8. PMID: 18209098.
15. Stoitzner P, Tripp CH, Eberhart A, Price KM, Jung JY, Bursch L, Ronchese F, Romani N. Langerhans cells cross-present antigen derived from skin. PNAS 2006 May 16;103(20):7783-8. PMID: 16672373.
16. Stoitzner P, Tripp CH, Douillard P, Saeland S, Romani N. Migratory Langerhans cells in mouse lymph nodes in steady state and inflammation. J Invest Dermatol 2005 Jul;125(1):116-25. PMID: 15982311.
17. Stoitzner P, Holzmann S, McLellan AD, Ivarsson L, Stössel H, Kapp M, Kämmerer U, Douillard P, Kämpgen E, Koch F, Saeland S, Romani N. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J Invest Dermatol 2003 Feb;120(2):266-74. PMID: 12542532.

Link to all publications:

stoitzner - Search Results - PubMed (nih.gov)

‪patrizia stoitzner - ‪Google Scholar

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Team

Prof. Patrizia Stoitzner, Head of Lab for Langerhans Cell Research

I studied Microbiology with focus on biochemistry at the University of Innsbruck and did my master and PhD thesis at the Department of Dermatology (Medical University of Innsbruck) on the migration of skin DC, the characterization of Langerin as a novel marker for Langerhans cells (LC) and the cross-presentation ability of LC.  During this time, we also developed novel immunization strategy through the skin and during my post doctoral fellowship at the Malaghan Institute of Medical Research (Wellington, New Zealand) we tested this novel vaccination approach in mouse tumor models. Since 2007, I am head of the Langerhans Cell Research Lab at the Department of Dermatology with a research focus on the role of skin DC in tumor immunity. In 2020, I was promoted to Full Professor for Experimental Dermatology with specialization in tumor immunology and since 2021 I am coordinator of the largest PhD-program (Molecular and Cellular Biology of Diseases/MCBD) at the Medical University of Innsbruck.

Christoph H. Tripp, PhD, Senior Staff Scientist

Christoph studied Microbiology at the University of Innsbruck and completed his master thesis on the ontogeny of LC in our lab at the Department of Dermatology. Subsequently he worked in his PhD thesis on the effects of toll-like receptor ligand application to the skin in a mouse model of DC vaccination. In 2012, he became senior staff scientist working on the characterization of immune infiltrates in patient tumor samples.

Claudia Zelle-Rieser, PhD, Senior post doc

Claudia studied Microbiology at the University of Innsbruck and since her PhD-thesis she has been working on DC biology and DC-based immunotherapy for cancer patients. She joined the lab in September 2018 to work on human DC- and LC-based immunotherapies. With her long-standing expertise in DC biology, she studies how targeting approaches boost antigen presentation by LC and supports us with developing novel immunocompetent 3D-bioprinted skin models.

Florian Hornsteiner, MSc, PhD student

Florian studied Molecular and Developmental Biology in Innsbruck and is currently finishing his PhD thesis with the topic "BRAF inhibitor-mediated effects on the immune system in melanoma mouse models”. He established a 26-marker panel to dissect the complex network of myeloid cells in skin and tumors and became a specialist in the analysis of multicolor flow cytometry. In his work, he wants to understand how DC contribute to cancer therapy with tumor-targeted therapy, e.g. BRAF-inhibitor.

Helen Strandt, PhD, postdoctoral fellow

Helen studied Biology at the University of Salzburg and investigated in her PhD-thesis self-antigen presentation by LC. She came to our lab in 2021 to work on projects to advance DC-based targeting approaches for skin immunization. Recently she received funding to set up her own project working on the role of inflammasome activation in LC during vitiligo pathogenesis.

Sophie Dieckmann, MSc, PhD student

Sophie studied Molecular Medicine in Tuebingen and started her PhD-thesis on the metabolic alterations in a spontaneous melanoma mouse model in the lab in 2021. She wants to understand how DC subsets change due to tumor metabolism and how metabolites affect their functional properties. With inhibitors for glutaminolysis she aims to develop combinations with DC-based immunotherapy.

Janine Vierthaler, MSc, PhD student

Janine studied Molecular Medicine in Innsbruck and finished her master thesis on "Unraveling the role of novel CD64+ DC population in transplantable melanoma” in our lab.  She now continues to work on the origin and functional properties of CD64+DC in tumor immunity.

Christina Mayerl, PhD, clinical research and biomedical assistant

Christina studied Medical Sciences in Innsbruck and joined our lab in 2022 to support our research lab. She works mainly on human skin preps and DC differentiation. We also profit from her longtime experience in supervising clinical trials and as lab manager. She is responsible for applications to the ethical committees and lab management.

Markus Kanduth, M.Sc., master student

Markus studied Molecular Medicine in Innsbruck and joined our lab recently to do his second master. He is working with Helen Strandt on establishing a novel mouse model for vitiligo and on investigating inflammasome activation in mouse and human skin DC.

Annelie Schäfer, B.Sc.

Annelie studied Molecular Medicine in Innsbruck and joined our lab recently for her master thesis. She is working together with Sophie Dieckmann on understanding "Inhibition of glutamate metabolism in tumor cells to treat melanoma" in a melanoma mouse model.

Nikolaus Romani, PhD, Professor emeritus:

Niki studied biology at the University of Innsbruck where he obtained his PhD in 1983. During his post doc time at the Rockefeller University in Ralph Steinman's laboratory (1987-88) he deepened his knowledge on DC biology and helped to make Innsbruck one of the first "dendritic cell strongholds" in the Old World (together with Gerold Schuler) thereafter. Since then he has pursued DC research with focus on investigating their functional properties to harness these cells for DC-based immunotherapy at our department. He was promoted to Full Professor for Experimental Dermatology in 2012 and emerited in October 2018.

Former lab members:

• Daniela Ortner-Tobider, post doc (2014-2021) working on carcinogen- and UVB-induced mouse tumor models to investigate the immunological process in early tumorigenesis.
• Sarah Bregar, master student (2021-2022): "Investigation of DC-T cell interactions during BRAF-inhibitor therapy of melanoma”
• Athanasios Seretis, PhD student (2016-2021): "Combination Therapies to Improve Dendritic Cell-based Treatment of Melanoma"
• Lydia Bellmann, PhD student (2016-2020): "Targeting antigens to C-type lectin receptors on human skin dendritic cells to enhance immune responses against cancer"
• Anastasia (Natasa) Prokopi, PhD student (2015-2020): "The duality of the immune system in melanoma"
• Kerstin Komenda, B.Sc., biomedical  assistant from 2013-2021
• Rita Steindl, master student (2019): "Combination therapy to improve DC-based treatment of melanoma”
• Giuseppe Cappellano, post doc (2017-2018) working on immune response in mouse melanoma models and DC-targeting approaches for combination therapy with BRAF-inhbitor.
• Johanna Schachtl-Riess, master student (2017-2018) "Dendritic cells and NK cells in tranasplatlabel melanoma mouse models”  
• Katharina Hutter, Master thesis (2016-2017) "Phenotypical and functional characterization of T cells in a spontaneous melanoma mouse model”
• David Mairhofer, PhD thesis (2011-2015): "Consequences of spontaneous mouse melanoma development on the immunological landscape”
• Hermann Voit, diploma student (2016-2017) "Establishmend and optimization of novel laser-based  treatments for immunotherapeutical applications”
• David Schlögl, diploma student (2013-2015) "Interaction of the immune system with tumor cells in an animal model for skin cancer: optimization of NK-cell staining”

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News

Congratulations Doctor Flo!

On the 21^st of March Florian Hornsteiner defended successfully his PhD-thesis.

And his paper on "Tumor-targeted therapy with BRAF-inhibitor recruits activated dendritic cells to promote tumor immunity in melanoma" was accepted at the Journal for ImmunoTherapy of Cancer.

Thanks Björn Clausen for visiting us as Flo's examiner and also presenting your latest exciting story on "Cracking the tubulin code of Langerhans cell and dendritic cell function".

Visit Giuseppe Cappellano, April 2023:

Our former post doc Assoc.Prof. Giuseppe Cappellano came to visit our lab and present his newest research on Covid and tumor immunity in a seminar called "Bad things come in three: ICOS/ICOSL/OPN trio in tumors"

Day of Immunology 2023:

"Vor zehn Jahren gab es bei Hautkrebs kaum Heilungschancen" - myPoint (i-med.ac.at)

Excellent Research at the Department of Dermatology in Innsbruck:

Several awards for the research work was awarded to the Lab for Langerhans Cell Research at the Annual Meeting of the ADF in February 2023:

Universitätsklinik für Dermatologie, Venerologie und Allergologie | News (tirol-kliniken.at)

Guidelines for DC protocols in Eur J Immunol published in 2022:

Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues - Probst - European Journal of Immunology - Wiley Online Library

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